Versatile Palladium-catalyzed intramolecular cyclization to access new luminescent azaphosphaphenalene motifs.

Using a straightforward sequence of diphosphonylation and a Pd-catalysed concerted-metalation-deprotonation (CMD), a synthetic strategy towards polyaromatic phosphorus containing heterocycles was developed. Herein, we report the synthesis and characterization of new azaphosphaphenalenes, using easily accessible palladium catalysts and starting materials. The key tetrahydroquinoline intermediates of the reaction were synthesised via a fast and effective procedure and could be isolated as such, or further reacted towards the target polyaromatic structures. The obtained products showed interesting luminescent properties and their emission, excitation and quantum yields were evaluated.

Co-Removal of Perfluorooctanoic Acid and Nitrate from Water by Coupling Pd Catalysis with Enzymatic Biotransformation.

PFAS (poly- and per-fluorinated alkyl substances) represent a large family of recalcitrant organic compounds that are widely used and pose serious threats to human and ecosystem health. Here, palladium (Pd0)-catalyzed defluorination and microbiological mineralization were combined in a denitrifying H2-based membrane biofilm reactor to remove co-occurring perfluorooctanoic acid (PFOA) and nitrate. The combined process, i.e., Pd-biofilm, enabled continuous removal of ∼4 mmol/L nitrate and ∼1 mg/L PFOA, with 81% defluorination of PFOA. Metagenome analysis identified bacteria likely responsible for biodegradation of partially defluorinated PFOA: Dechloromonas sp. CZR5, Kaistella koreensis, Ochrobacterum anthropic, and Azospira sp. I13. High-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and metagenome analyses revealed that the presence of nitrate promoted microbiological oxidation of partially defluorinated PFOA. Taken together, the results point to PFOA-oxidation pathways that began with PFOA adsorption to Pd0, which enabled catalytic generation of partially or fully defluorinated fatty acids and stepwise oxidation and defluorination by the bacteria. This study documents how combining catalysis and microbiological transformation enables the simultaneous removal of PFOA and nitrate.

Enhanced Selectivity in 4-Quinolone Formation: A Dual-Base System for Palladium-Catalyzed Carbonylative Cyclization with Fe(CO)5.

The use of gaseous CO in Pd-catalyzed carbonylative quinolone synthesis presents challenges related to safety and precise pressure control. In response, a streamlined non-gaseous synthesis of 4-quinolone compounds has been developed. This study introduces a tunable CO-releasing system utilizing Fe(CO)5 activated by a dual-base system of piperazine and triethylamine. This alternative liquid CO resource facilitates the palladium-catalyzed carbonylative C-C coupling and subsequent intramolecular cyclization. By tuning the tandem kinetics of carbonylation and cyclization, this non-gaseous method achieves the successful synthesis of 22 distinct 4-quinolones with excellent yields. This is achieved through the three-component condensation of sub-stoichiometric amounts of Fe(CO)5 with 2-iodoaniline and terminal alkynes. Operando mechanistic studies have revealed a novel CO transfer mechanism that facilitates homogeneous carbonylative cyclization, distinguishing this method from traditional techniques. In addition to addressing safety concerns, this approach also provides precise control over selectivity, with significant implications for pharmaceutical research and the efficient synthesis of pharmaceutical and bioactive compounds.

Enantioselective Arylation of Sulfenamides to Access Sulfilimines Enabled by Palladium Catalysis.

Sulfur-containing functional groups have garnered considerable attention due to their common occurrence in ligands, pharmaceuticals, and insecticides. Nevertheless, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging and persistent goal. Herein we report a highly enantio- and chemoselective cross-coupling of sulfenamides with aryl diazonium salt to construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide groups play a crucial role in achieving high reactivity and selectivity. This approach provides a general, modular and divergent framework for quickly synthesizing chiral sulfilimines and sulfoximines that are otherwise challenging to access. In addition, the origins of the high chemoselectivity and enantioselectivity were extensively investigated using density functional theory calculations.

Ligand-Enabled Pd-Catalyzed sp3 C‒H Macrocyclization: Synthesis and Evaluation of Macrocyclic Sulfonamide for the Treatment of Parkinson's Disease.

The development of simplified synthetic strategy to create structurally and functionally diverse pseudo-natural macrocyclic molecules is highly appealing but poses a marked challenge. Inspired by natural scaffolds, herein, we describe a practical and concise ligand-enabled Pd(II)-catalysed sp3 C‒H alkylation, olefination and arylation macrocyclization, which could offer a novel set of pseudo-natural macrocyclic sulfonamides. Interestingly, the potential of ligand acceleration in C‒H activation is also demonstrated by an unprecedented enantioselective sp3 C‒H alkylation macrocyclization. Moreover, a combination of in silico screening and biological evaluation led to the identification of a novel spiro-grafted macrocyclic sulfonamide 2a, which showed a promising efficacy for the treatment of Parkinson's disease (PD) in a mouse model through the activation of silent information regulator sirtuin 3 (SIRT3).

Picolinaldehyde-Zinc(II)-Palladium(0) Catalytic System for the Asymmetric α-Allylation of N-Unprotected Amino Esters.

Reported in this work is a synergistic ternary achiral picolinaldehyde-Zn(II)-chiral palladium complex system for the highly enantioselective α-allylation of N-unprotected amino esters. By utilizing a variety of allylic carbonates or vinyl benzoxazinanones as substrates, α-allyl α-amino esters were obtained in high yields (up to 96 %) with high enantioselectivities (up to 98 % ee). Control experiments suggest that the coordination of Zn(II) with the Schiff base intermediate enhances the acidity of the α-C-H bonds of amino esters, thereby favoring α-allylation over intrinsic N-allylation. Furthermore, NMR studies reveal an interaction between the chiral palladium complex and the Zn(II)-Schiff base intermediate, leading to the formation of a picolinaldehyde-Zn(II)-Pd(0) catalytic system.

Coremoval of Energetics and Oxyanions via the In Situ Coupling of Catalytic and Enzymatic Destructions: A Solution to Ammunition Wastewater Treatment.

Ammunition wastewater contains toxic nitrated explosives like RDX and oxyanions like nitrate and perchlorate. Its treatment is challenged by low efficiency due to contaminant recalcitrance and high cost due to multiple processes needed for separately removing different contaminant types. This paper reports a H2-based low-energy strategy featuring the treatment of explosives via catalytic denitration followed by microbial mineralization coupled with oxyanion reduction. After a nitrate- and perchlorate-reducing biofilm incapable of RDX biodegradation was coated with palladium nanoparticles (Pd0NPs), RDX was rapidly denitrated with a specific catalytic activity of 8.7 gcat-1 min-1, while biological reductions of nitrate and perchlorate remained efficient. In the subsequent 30-day continuous test, >99% of RDX, nitrate, and perchlorate were coremoved, and their effluent concentrations were below their respective regulation levels. Detected intermediates and shallow metagenome analysis suggest that the intermediates after Pd-catalytic denitration of RDX ultimately were enzymatically utilized by the nitrate- and perchlorate-reducing bacteria as additional electron donor sources.

Cooperative Chiral Lewis Base/Palladium-Catalyzed Asymmetric Syntheses of Methylene-Containing δ-Lactams.

We herein report a two-step approach for the enantioselective synthesis of novel chiral δ-lactams. By using a cooperative chiral ITU/achiral Pd-catalyst system, this protocol proceeds via an asymmetric α-allylation of activated aryl esters first, followed by an acid-mediated lactam formation. A variety of differently substituted products could be obtained with usually high levels of enantioselectivities and in reasonable yields (16 examples, up to 98 : 2 er and 73 % yield over two steps). In addition, further utilizations of the products via transformations of the exocyclic double bond were successfully carried out as well.

O- and N-Selective Electrophilic Activation of Allylic Alcohols and Amines in Pd-Catalyzed Direct Alkylation.

Catalytic control of chemoselectivity is crucial in the synthesis of highly functionalized compounds. Although there are reports of efficient chemoselective reactions of alcohols and amines as nucleophiles, there are no reports of the chemoselective activation of alcohols and amines as electrophiles. In this study, highly O- and N-selective electrophilic activation of allylic alcohols and amines was achieved in Pd-catalyzed direct allylic alkylation. Allylamines were inherently more reactive than allylic alcohols (N-selectivity). On the other hand, the addition of catalytic amounts of 9-phenanthreneboronic acid preferentially activated allylic alcohols over allylamines (O-selectivity). Density functional theory (DFT) calculations suggested that the N-selectivity is due to the selective activation of allylic amines with ammonium cations, and boronate formation accelerates the activation of allylic alcohols.

Polyoxa- and Polyazamacrocycles Incorporating 6,7-Diaminoquinoxaline Moiety: Synthesis and Application as Tunable Optical pH-Indicators in Aqueous Solution.

Synthetic approach to fluorescent polyaza- and polyoxadiazamacrocycles comprising a structural fragment of 6,7-diamino-2,3-diphenylquinoxaline has been elaborated using Pd-catalyzed amination providing target compounds in yields up to 77%. A series of nine novel N- and N,O-containing macrocyclic ligands differing by the number of donor sites and cavity size has been obtained. These compounds possess well-pronounced fluorescent properties with emission maxima in a blue region in aprotic solvents and high quantum yields of fluorescence, while in proton media, fluorescence shifts towards the green region of the spectrum. Using macrocycles 5c and 5e as examples, we have shown that such compounds can serve as dual-channel (colorimetric and fluorimetric) pH indicators in water media, with pH transition point and response being dependent on the macrocycle structure due to different sequences of protonation steps.

Palladium-Catalyzed Stereoselective Construction of 1,3-Stereocenters Displaying Axial and Central Chirality via Asymmetric Alkylations.

The concurrent construction of 1,3-stereocenters remains a challenge. Herein, we report the development of stereoselective union of a point chiral center with allenyl axial chirality in 1,3-position by Pd-catalyzed asymmetric allenylic alkylation between racemic allenyl carbonates and indanone-derived ß-ketoesters. Various target products bearing a broad range of functional groups were afforded in high yield (up to 99%) with excellent enantioselectivities (up to 98% ee) and good diastereoselectivities (up to 13:1 dr).

Facile Attachment of Halides and Pseudohalides to Dodecaborate(2-) via Pd-catalyzed Cross-Coupling.

Cross-coupling reactions with [B12H11I]2- as one partner have been used successfully for Kumada and Buchwald Hartwig couplings with Pd catalysis. Here, we found that the iodide could be substituted easily, and unexpectedly, with other halides such as Br and Cl, and with pseudohalides such as cyanide, azide, and isocyanate. We found that for Cl, Br, N3, and NCO, tetrabutylammonium salts-or sodium salts-were successful halide sources, whereas for cyanide, CuCN was the only halide source that allowed a successful exchange. The azide could be reacted further in a click reaction with triazoles. While no substitution with fluoride occurred, tetrabutylammonium fluoride in the presence of water led to [B12H11OH]2-. Yields were high to very high, and reaction times were short when using a microwave oven as a heating source.

Synergistic Palladium/Lewis Acid-Catalyzed Regio- and Stereo-divergent Bissilylation of Alkynoates: Scope, Mechanism, and Origin of Selectivity.

Transition metal-catalyzed bissilylation reactions of alkynes with disilane reagents have become one of the most straightforward and efficient protocols to rapidly produce structurally diverse alkenyl silicon derivatives. In these reactions, the utilization of unsymmetrical disilane reagents provided the possibilities for reactivity enhancement as well as the synthetic merits in contrast to symmetrical disilane reagents. However, a major yet challenging objective is achieving precise control over the selectivity including the regioselectivity and the cis/trans-selectivity. Herein we realized the first divergent bissilylation of alkynoates with our developed air-stable disilane reagent 8-(2-substituted-1,1,2,2-tetramethyldisilanyl)quinoline (TMDQ) by means of synergistic Pd/Lewis acid catalytic system. The catalytic system precisely dictates the selectivity, resulting in the divergent synthesis of 1,2-bissilyl alkenes. The power of these 1,2-bissilyl alkenes serving as the key synthetic intermediates has been clearly demonstrated by rapid construction of diverse motifs and densely functionalized biologically active compounds. In addition, the origins of the switchable selectivities were well elucidated by experimental and computational studies on the reaction mechanism and were mainly attributed to different ligand steric effects, the use of the specific disilane reagent TMDQ and the different coordination modes of different Lewis acid with alkynoates.

Asymmetric (4+1) Annulations by Cascade Allylation and Transient σ-Alkyl-Pd(II) Initiated Allylic Csp3 -H Activation.

A unique Pd-catalyzed approach for asymmetric (4+1) annulations via cascade allylation and transient σ-alkyl-Pd(II) initiated methylene Csp3 -H activation is reported. The enolate fragment derived from the decarboxylation of vinyl methylene carbonate is crucial to stabilize the key intermediate. These reactions enable the synthesis of various useful dihydrobenzofurans with excellent enantioselectivity, typically >95 : 5 er, and exclusive (Z)-stereoselectivity. Compared with the well-established annulations via Heck-type C-H activations, this protocol showcases a conceptually new way to generate σ-alkyl-Pd(II) species that could initiate challenging asymmetric Csp3 -H activations.

The Aryl Sulfide Synthesis via Sulfide Transfer.

Aryl sulfides are in great demands in drugs and materials sciences. To avoid using nucleophilic and noxious thiols, many efforts have been focused on exploring novel sulfide resources. Herein, a reductive Pd-catalyzed, Ni-mediated method to synthesize aryl sulfides via a sulfide transfer reaction is developed. The utility and scope of this reaction is exemplified by various aryl electrophiles and aryl sulfides. Mechanistic studies reveal two competing catalytic cycles of sulfide transfer and aryl transfer in this reaction, where the former one is favored over the later one because of the large energy barrier difference during the transmetalation. Moreover, two important chemicals are late-stage functionalized by this method, exhibiting the potential applications in drugs and materials science.

Isoselective Hydroformylation of Propylene by Iodide-Assisted Palladium Catalysis.

Isobutanal is a high value bulk material that, in principle, could be produced with 100 % atom-economy by isoselective hydroformylation of propylene with syngas. However, leading industrial Rh- and Co-catalyzed hydroformylation methods preferentially form n-butanal over the iso-product, and methods offering isoselectivity remain underdeveloped. Here we report an iodide-assisted Pd-catalyzed hydroformylation of propylene that produces isobutanal with unprecedented levels of selectivity. The method involves PdI2 , simple alkyl monophosphines, such as tricyclohexylphosphine, and common green solvents, enabling the title reaction to occur with isoselectivity in up to 50 : 1 iso/n product ratios under industrially relevant conditions (80-120 °C). The catalytic and preliminary mechanistic experiments indicate a key role of the iodide anions in both the catalytic activity and the isoselectivity.

Picolinamides and Iodoalkynes Enable Palladium-Catalyzed syn-Aminoalkynylation of Di- and Trisubstituted Alkenes to Give Pyrrolidines.

Palladium-catalyzed aminoalkynylation of electronically unbiased olefins with iodoalkynes is reported. The picolinamide auxiliary enables for the first time the syn-selective aminoalkynylation of mono-, di- and trisubstituted alkenes to afford the corresponding pyrrolidines in up to 97 % yield and as single diastereomers. Furthermore, through a C-H activation approach, the picolinamide allows the rapid synthesis of functionalized olefins, which are suitable cyclization precursors. Facile and orthogonal deprotection of the amides and Sii Pr3 -acetylenes in the products, and a subsequent Pictet-Spengler reaction is demonstrated.

Palladium-Catalyzed Silylacylation of Allenes Using Acylsilanes.

We have developed a palladium-catalyzed addition of a C-Si bond of acylsilanes across a range of unactivated allenes. The reaction proceeds with complete regioselectivity, in which a silyl group binds to the central carbon of the allene, allowing for the straightforward access to functionalized alkenylsilane derivatives.

ppm Pd-Containing Nanoparticles as Catalysts for Negishi Couplings in Water.

New technology is reported that enables Negishi couplings to be run under sustainable, far greener conditions. Thus, ppm Pd-containing nanoparticles (NPs) have been developed that catalyze couplings in recyclable water under very mild conditions. These heterogeneous reactions involve loadings of Pd of typically only 2500 ppm (0.25 mol %). Highly functionalized aromatic and heteroaromatic bromides readily participate, including examples taken from the Merck Informer Library indicative of the functional group tolerance associated with these couplings. Direct comparisons with existing literature routes are made. Very low residual levels of Pd in newly formed products are to be expected, as determined by ICP-MS. The reagent involved has been extensively characterized via DLS, TEM, cryo-TEM, and EDX measurements.

Alkyne Aminopalladation/Heck and Suzuki Cascades: An Approach to Tetrasubstituted Enamines.

Alkyne aminopalladation reactions starting from tosylamides are reported. The emerging vinylic Pd species are converted either in an intramolecular Heck reaction with olefinic units or in an intermolecular Suzuki reaction by using boronic acids exhibiting broad functional group tolerance. Tetra(hetero)substituted tosylated enamines are obtained in a simple one-pot process.